Steroidal C-21 heteroaryl thioethers (Part 2): discovery of orally bioavailable selective glucocorticoid receptor modulators (dissociated steroids)

  • Bioorg Med Chem Lett. 2012 Jan 15;22(2):1086-90. doi: 10.1016/j.bmcl.2011.11.120.
Purakkattle Biju  1 ,  Kevin McCormick ,  Robert Aslanian ,  Michael Berlin ,  Daniel Solomon ,  Hongwu Wang ,  Yoon Joo Lee ,  Rema Bitar ,  Daniel Prelusky ,  Robbie McLeod ,  Yanlin Jia ,  Xiomora Fernandez ,  Stephen Eckel ,  Aileen House ,  Gissela Lieber ,  Johanna Jimenez ,  George Kelly ,  Richard Chapman ,  Jonathan Phillips ,  John Anthes
Affiliations
  • 1. Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. [email protected]
PMID: 22197391 DOI: 10.1016/j.bmcl.2011.11.120
Abstract

The prednisolone C-21 heteroaryl thioethers have been synthesized and evaluated in cell based transrepression and transactivation assays. Most of the compounds demonstrated weak transactivational activity in both human and rat tyrosineaminotransferase functional assay while keeping potent anti-inflammatory activity. The benzimidazole thioether 7 exhibited comparable anti-inflammatory activity and improved safety profile compared to the classical oral steroid prednisolone.